Epigenetic control of the germinal center reaction and lymphomagenesis
The majority of B-cell lymphomas, including FL and DLBCL, arise from germinal center (GC) B-cells, and are characterized by somatic mutations in histone modifying enzymes. A critical phase in the GC B-cell reaction is the signaling of T-cells to B-cells to exit the GC through a series of signaling molecules, referred to as the ‘Immune Synapse’.
“Epigenetic disruption of the ‘Immune Synapse’ is a crucial initiating event for most GC derived lymphomas”, Professor Ari Melnick (Weil Cornell Medical College, New York, US) explained in a Basic Science-in-Focus session. He presented an excellent overview of recent studies demonstrating that the epigenetic mutations have two types of effects: unleashing B-cells from restraints on growth and survival, and enabling B-cells to hide from T-cell immune surveillance. Epigenetic targeted therapies may restore the function of the ‘Immune Synapse’.